Sodium hydride → HCID 66584503, compound

HRID 1525636Notes

Reaction equation

HRID 1525636 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:16][CH:15]=2)[CH2:11][C@@H:10]([CH3:26])[C:9]1=[O:27])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1([Se]Br)C=CC=CC=1>C1(C)C=CC=CC=1.O>[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[CH:18][CH:19]=2)[CH:11]=[C:10]([CH3:26])[C:9]1=[O:27])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 123446BromoselenobenzeneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 66739124(3R,5S)-5-biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 66584503HCID 66584503, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
-15 °C

Procedure

3.65 g (3R,5S)-5-Biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (3-a, R1=Boc) is added to toluene (20 ml). Sodium hydride (400 mg) is added to the mixture. The mixture is cooled to −15° C. 22 ml Potassium bis(trimethylsilyl)amide (0.5 M solution in toluene) is then added. The resulting mixture is then stirred for 1 h at −15° C. Phenylselenyl bromide (2.8 g) in toluene (20 ml) is then added to the mixture. The resulting mixture is stirred for 0.5 h at −15° C. The mixture is then poured into water and the phases are separated. The organic phase is concentrated under reduced pressure. Ethyl acetate (50 ml) and aqueous hydrogen peroxide (10 ml, 30%) is then added to the residue at ambient temperature. After 1 h of stirring, the phases are separated. The organic phase is washed with saturated sodium hydrogen carbonate solution, and then saturated sodium hydrogen sulfite solution, before being concentrated under reduced pressure. The residue is crystallised from isopropyl acetate/heptane (20 ml:5 ml) to afford (R)-5-biphenyl-4-ylmethyl-3-methyl-2-oxo-2,5-dihydro-pyrrole-1-carboxylic acid tert-butyl ester (4a, R1=Boc). 1H NMR (DMSO): 1.56 (9H), 1.66 (3H), 3.02 (1H), 3.32 (1H), 4.75 (1H), 7.04 (1H), 7.18 (2H), 7.36 (1H), 7.46 (2H), 7.60 (2H), 7.66 (2H).

Workup

  1. stirringThe resulting mixture is stirred for 0.5 h at −15° C
  2. customthe phases are separated
  3. concentrationThe organic phase is concentrated under reduced pressure
  4. additionEthyl acetate (50 ml) and aqueous hydrogen peroxide (10 ml, 30%) is then added to the residue at ambient temperature
  5. stirringAfter 1 h of stirring
  6. customthe phases are separated
  7. washThe organic phase is washed with saturated sodium hydrogen carbonate solution
  8. concentrationsaturated sodium hydrogen sulfite solution, before being concentrated under reduced pressure
  9. customThe residue is crystallised from isopropyl acetate/heptane (20 ml:5 ml)

Sources & evidence

ORD record
ord-681550a3c833452aa56c35f671b5fffe
Source dataset
uspto-grants-2015_07
Patent number
US09085529B2

Reaction notes

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